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Details

Stereochemistry ACHIRAL
Molecular Formula C45H50ClN7O7S
Molecular Weight 868.439
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VENETOCLAX

SMILES

CC1(C)CCC(CN2CCN(CC2)C3=CC=C(C(=O)NS(=O)(=O)C4=CC=C(NCC5CCOCC5)C(=C4)[N+]([O-])=O)C(OC6=CN=C7NC=CC7=C6)=C3)=C(C1)C8=CC=C(Cl)C=C8

InChI

InChIKey=LQBVNQSMGBZMKD-UHFFFAOYSA-N
InChI=1S/C45H50ClN7O7S/c1-45(2)15-11-33(39(26-45)31-3-5-34(46)6-4-31)29-51-17-19-52(20-18-51)35-7-9-38(42(24-35)60-36-23-32-12-16-47-43(32)49-28-36)44(54)50-61(57,58)37-8-10-40(41(25-37)53(55)56)48-27-30-13-21-59-22-14-30/h3-10,12,16,23-25,28,30,48H,11,13-15,17-22,26-27,29H2,1-2H3,(H,47,49)(H,50,54)

HIDE SMILES / InChI

Description

Venetoclax (trade name Venclexta, also known as ABT-199) is a selective and orally bioavailable small-molecule inhibitor of BCL-2, an antiapoptotic protein. BCL-2 and its related proteins BCL-XL and MCL-1 bind to and sequester pro-apoptotic signals in the cell, causing a down-regulation of apoptosis. As an oncogene and an important regulator of apoptosis, BCL-2 overexpression therefore results in increased tumor cell survival and resistance to chemotherapy. FDA approved Venetoclax in April 2016 for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by an FDA approved test, who have received at least one prior therapy. Also this drug in phase 3 clinical trial in combination therapy for the treatment patients with refractory myeloma and Acute Myeloid Leukemia. Common side effects include neutropenia, nausea, anemia, diarrhea, upper respiratory tract infection. Major side effects include tumor lysis syndrome and severe neutropenia.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
VENCLEXTA
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
2.1 μg/mL
400 mg 1 times / day steady-state, oral
VENETOCLAX plasma
Homo sapiens
1.43 μg/mL
400 mg 1 times / day multiple, oral
VENETOCLAX plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
32.8 μg × h/mL
400 mg 1 times / day steady-state, oral
VENETOCLAX plasma
Homo sapiens
30.2 μg × h/mL
400 mg 1 times / day multiple, oral
VENETOCLAX plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
14.1 h
400 mg 1 times / day multiple, oral
VENETOCLAX plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
400 mg 1 times / day steady-state, oral
VENETOCLAX plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
Initiate therapy with VENCLEXTA (venetoclax) at 20 mg once daily for 7 days, followed by a weekly ramp-up dosing schedule to the recommended daily dose of 400 mg. VENCLEXTA tablets should be taken orally once daily with a meal and water.
Route of Administration: Oral
In Vitro Use Guide
ABT-199 (Venetoclax) shows less sensitivity to Bcl-xL, Mcl-1 and Bcl-w with Ki of 48 nM, > 444 nM and 245 nM, respectively. ABT-199 potently inhibits FL5.12-Bcl-2 cells, RS4;11 cells with EC50 of 4 nM and 8 nM, while shows low activity against FL5. ABT-199 also induces apoptosis in CLL with an average EC50 of 3.0 nM.